TY - JOUR
T1 - Expression of Thymidine Kinase Is Essential to Low Dose Radiation Resistance of Rat Glioma Cells
AU - Al-Nabulsi, Isaf
AU - Voloshin, Yaroslav
AU - Dritschilo, Anatoly
AU - Jorgensen, Timothy J.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1994/11
Y1 - 1994/11
N2 - We have found that thymidine kinase expression is a major radioresponse determinant in rat glioma cells. Cells that lack thymidine kinase expression are significantly more radiosensitive relative to the wild-type cells. The degree of sensitization is large, particularly at the dose levels used in fractionated radiotherapy. The difference in low dose survival can be accounted for by a marked difference in the ability of the cells to undergo repair of sublethal damage. When herpes thymidine kinase was introduced into the thymidine kinase-deficient mutant cells, radioresistance was partially restored, and sublethal damage repair was also enhanced. All other radiobiological responses, including DNA double-strand break repair, potentially lethal damage repair, G2 arrest, and cell cycle distribution, appeared similar among the cell lines. These data suggest that the thymidine kinase enzyme or its cellular gene may be an excellent therapeutic target to increase radiosensitivity and thereby, to enhance the radiocurability of malignant brain gliomas.
AB - We have found that thymidine kinase expression is a major radioresponse determinant in rat glioma cells. Cells that lack thymidine kinase expression are significantly more radiosensitive relative to the wild-type cells. The degree of sensitization is large, particularly at the dose levels used in fractionated radiotherapy. The difference in low dose survival can be accounted for by a marked difference in the ability of the cells to undergo repair of sublethal damage. When herpes thymidine kinase was introduced into the thymidine kinase-deficient mutant cells, radioresistance was partially restored, and sublethal damage repair was also enhanced. All other radiobiological responses, including DNA double-strand break repair, potentially lethal damage repair, G2 arrest, and cell cycle distribution, appeared similar among the cell lines. These data suggest that the thymidine kinase enzyme or its cellular gene may be an excellent therapeutic target to increase radiosensitivity and thereby, to enhance the radiocurability of malignant brain gliomas.
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M3 - Article
C2 - 7923206
AN - SCOPUS:0027988163
SN - 0008-5472
VL - 54
SP - 5614
EP - 5617
JO - Cancer Research
JF - Cancer Research
IS - 21
ER -